Mechanism of folding chamber closure in a group II chaperonin. Nature 463:379–383. doi: 10.1038/nature08701

Group II chaperonins are essential mediators of cellular protein folding in eukaryotes and archaea. These oligomeric protein machines, ~1MDa, consist of two back-to-back rings encompassing a central cavity that accommodates polypeptide substrates1,2,3. Chaperonin-mediated protein folding is critically dependent on the closure of a built-in lid4,5, which is triggered by ATP hydrolysis6. The structural rearrangements and molecular events leading to lid closure are still unknown. Here, we report four single particle cryo-EM structures of Mm-cpn, an archaeal group II chaperonin5,7, in the nucleotide-free (open) and nucleotide-induced (closed) states. The 4.3 Å resolution of the closed conformation allowed building of the first ever atomic model directly from the cryo-EM density map, in which we were able to visualize the nucleotide and over 70 % of the sidechains. The model of the open conformation was obtained by using the deformable elastic network modeling with the 8 Å resolution open state cryo-EM density restraints. Together, the open and closed structures reveal how local conformational changes triggered by ATP hydrolysis lead to an alteration of intersubunit contacts within and across the rings, ultimately causing a rocking motion that closes the ring. Our analysis reveals an intricate and unforeseen set o